Dr. Richard Peltier's long term career goal is to become an independent investigator capable of leading advanced aerosol exposure assessment research that makes a purposeful contribution to understanding exposures and their specific health effects. During the mentored research phase (K99), Dr. Peltier will gain expertise in conducting spatial epidemiological analyses, working with national health information datasets, refining novel approaches to exposure assessment, and developing a better understanding of the health implications associated with exposure to fine particle nickel. Dr. Lung Chi Chen will serve as the primary mentor and oversee all aspects of the candidate's transition to an independent researcher. In addition, a team of 3 co-mentors will provide the candidate with complementary research approaches which will greatly enhance and diversify the candidate's research skill set. Together, the team of mentors has pledged to guide the candidate to extend his research interests and approaches, and to ensure a successful transition to an independent researcher. During the independent phase (R00) of this award, the candidate will conduct a series of in-vivo exposure studies on a murine model of cardiovascular disease. A variety of combustion emissions aerosol, which include enhancements with fine particle nickel, and processed by varying degrees of photochemistry, will be used to address health outcomes associated with exposure to fine particle aerosol. This work will lead to a better mechanistic understanding, with a particular focus on nickel and organic carbon aerosol, of the oxidative stress associated with fine particle exposures, and will lead to a better coupling of in-vivo exposure and broader scale epidemiological surveillance initiatives.